ABSTRACT Oral pre-exposure prophylaxis (PrEP) is a recommended component of combination HIV prevention by the World Health Organization and an approved biomedical intervention in many countries. In sub-Saharan Africa, young women are a priority population for HIV prevention and targeted to initiate PrEP, given the recent high rates of HIV incidence among women and urgent needs for strategies that do not require the engagement of male partners. A key question in the field is whether young women initiating PrEP have ongoing HIV risk and adhere to PrEP sufficiently to have protection from HIV when they have condomless sex with HIV- infected partners. The primary objective of this proposal is to leverage an existing cohort of young women using pre-exposure prophylaxis (PrEP) in Uganda to conduct objective measurement of HIV risk and determine whether women?s use of PrEP aligns with their true risk for acquiring HIV. To achieve our aims, we will collect samples and conduct laboratory assays to determine whether women in our ongoing cohort have: 1) detectable Y chromosome DNA (indicating exposure to semen in the past week) and/or 2) infection with common curable bacterial sexually transmitted infections N. gonorrhoeae or C. trachomatis, either are indications of HIV risk. We will also initiate recruitment and follow up of young men who are sexual partners of the women to determine whether the young men are infected with N. gonorrhoeae, C. trachomatis or HIV. We will use novel methods to recruit young men including the provision of HIV self-test kits through their female partners. These new measures of HIV risk will be merged with already collected data on tenofovir concentration in blood and daily pill box openings, objective measures of PrEP use. We have specified the following aims: 1) To determine whether young women?s adherence to PrEP aligns with HIV risk using objective measures of PrEP adherence and HIV risk and 2) To determine whether young women?s adherence to PrEP aligns with the HIV status and risk of their male partners. Impact. Objective measurement of HIV risk and the engagement of young women?s male partners is the only true way to know the HIV risk of women. Our study will provide a framework for understanding how and when young women decide to take PrEP, estimate the proportion of women that are benefitting from HIV protection when they have male partners with or at high risk of acquiring HIV, and provide novel opportunity to engage young men in PrEP delivery and as supporters of women?s PrEP use.